Aminoglycoside antibiotics are a well-known class of antibiotics with an established record of both efficacy and safety. These compounds are used largely for gram-negative bacteria but are also broad spectrum antibiotics with little resistance developed at this point. Patients treated with aminoglycoside antibiotics include immune compromised patients, such as newborns and their mothers, and cystic fibrosis patients. Aminoglycosides are also used as preservatives.
The primary use-limiting adverse reactions associated with the class are ototoxicity and nephrotoxicity. See, e.g., Rizzi and Hirose, Curr Opin Otolaryngol Head Neck Surg 15:352-357, 2007. Despite their ototoxic and nephrotoxic effects, aminoglycoside antibiotics remain one of the most widely used antibiotics worldwide.
Given the importance of aminoglycosides in treating multiple infections, new aminoglycosides having reduced ototoxicity and/or nephrotoxicity are needed. The present invention addresses these needs.